Emerging Technologies to Study Long Non-coding RNAs

  • Fereshteh Jahaniani
  • Varsha Rao
  • Stephanie Nevins
  • Damek Spacek
  • Neal Bharadwaj
  • Jason Reuter
  • Michael Snyder


It has been less than half a century since Robert W. Holley et al. used 140 kg of commercial baker’s yeast to characterize the first noncoding RNA (ncRNA), alanine tRNA. Now, 48 years later, advancements in genomic technologies have enabled scientists to study genomes, transcriptomes, and proteomes, on an unprecedented and high-throughput scale, and even at the single cell resolution. These discoveries have completely changed the classical view of the central dogma of molecular biology, as we now understand that protein coding genes account for less than 2 % of human genome, however, the vast majority of the genome is transcribed (Clark et al. 2011) {Lander, 2001 #41}. This means that the bulk of the genome encodes for ncRNA molecules, which can be further categorized into housekeeping and regulatory ncRNAs. The latter can be broadly classified based on their size as small ncRNAs (< 200 bp) and long noncoding RNAs (lncRNAs) (> 200 bp) (Nagano and Fraser 2011; Ponting et al. 2009). Many of the small ncRNAs have been identified and their mechanism of action has been heavily studied. However, the journey to study the lncRNAs has just begun (Gupta et al. 2010; Wilusz et al. 2009; Derrien et al. 2012).


Copy Number Variation Tiling Array lncRNA Expression lncRNA Gene Small ncRNAs 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Clark, M. B., et al. (2011). The reality of pervasive transcription. PLoS Biology, 9, e1000625; discussion e1001102. Google Scholar
  2. Friedman J.M., et al. (2006). Oligonucleotide microarray analysis of genomic imbalance in children with mental retardation. Am J Hum Genet. 79, 500. Google Scholar
  3. Nagano, T., & Fraser, P. (2011). No-nonsense functions for long noncoding RNAs. Cell, 145, 178. Google Scholar
  4. Ponting, C. P., Oliver, P. L., & Reik, W. (2009). Evolution and functions of long noncoding RNAs. Cell, 136, 629.Google Scholar
  5. Gupta, R. A., et al. (2010). Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature, 464, 1071.Google Scholar
  6. Wilusz, J. E., Sunwoo, H., & Spector, D. L., (2009). Long noncoding RNAs: functional surprises from the RNA world. Genes & Development 23, 1494.Google Scholar
  7. Derrien, T., et al. (2012). The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Research, 22, 1775.Google Scholar
  8. Brown, C. J., et al. (1991). A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature, 349, 38.Google Scholar
  9. Kampa, D., et al. (2004) Novel RNAs identified from an in-depth analysis of the transcriptome of human chromosomes 21 and 22. Genome Research, 14, 331.Google Scholar
  10. Cheng, J., et al. (2005). Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution. Science, 308, 1149.Google Scholar
  11. Rinn, J. L., et al. (2007). Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell, 129, 1311.Google Scholar
  12. Bernstein, E., & Allis, C. D. (2005). RNA meets chromatin. Genes & Development, 19, 1635.Google Scholar
  13. Plath, K., et al. (2003). Role of histone H3 lysine 27 methylation in X inactivation. Science, 300, 131.Google Scholar
  14. Kretz, M., et al. (2013). Control of somatic tissue differentiation by the long non-coding RNA TINCR. Nature, 493, 231.Google Scholar
  15. Batista, P. J., & Chang, H. Y. (2013). Long noncoding RNAs: cellular address codes in development and disease. Cell, 152, 1298.Google Scholar
  16. Clemson, C. M., et al. (2009). An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles. Molecular Cell, 33, 717.Google Scholar
  17. Willingham, A. T., et al. (2005) A strategy for probing the function of noncoding RNAs finds a repressor of NFAT. Science, 309, 1570.Google Scholar
  18. Jiang, L., Duan, D., Shen, Y., & Li, J. (2012). Direct microRNA detection with universal tagged probe and time-resolved fluorescence technology. Biosensors & Bioelectronics, 34, 291.Google Scholar
  19. Tang, X., et al. (2007). A simple array platform for microRNA analysis and its application in mouse tissues. Rna, 13, 1803.Google Scholar
  20. Benes, V., & Castoldi, M. (2010). Expression profiling of microRNA using real-time quantitative PCR, how to use it and what is available. Methods, 50, 244.Google Scholar
  21. Nagalakshmi, U., et al. (2008). The transcriptional landscape of the yeast genome defined by RNA sequencing. Science, 320, 1344.Google Scholar
  22. Mortazavi, A., Williams, B. A., McCue, K., Schaeffer, L., & Wold, B. (2008). Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nature Methods, 5, 621.Google Scholar
  23. Wang, Z., Gerstein, M., & Snyder, M. (2009). RNA-Seq: a revolutionary tool for transcriptomics. Nature Reviews. Genetics, 10, 57.Google Scholar
  24. Cabili, M. N., et al. (2011). Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes & Development, 25, 1915.Google Scholar
  25. Mercer, T. R., Dinger, M. E., Sunkin, S. M., Mehler, M. F., & Mattick, J. S. (2008). Specific expression of long noncoding RNAs in the mouse brain. Proceedings of the National Academy of Sciences of the United States of America, 105, 716.Google Scholar
  26. Gall, J. G., & Pardue, M. L. (1969). Formation and detection of RNA-DNA hybrid molecules in cytological preparations. Proceedings of the National Academy of Sciences of the United States of America, 63, 378.Google Scholar
  27. Chisholm, K. M., et al. (2012). Detection of long non-coding RNA in archival tissue: correlation with polycomb protein expression in primary and metastatic breast carcinoma. PLoS ONE, 7, e47998.PubMedCrossRefGoogle Scholar
  28. Rapicavoli, N. A., Poth, E. M., Zhu, H., & Blackshaw, S. (2011). The long noncoding RNA Six3OS acts in trans to regulate retinal development by modulating Six3 activity. Neural development, 6, 32.PubMedCrossRefGoogle Scholar
  29. Taft, R. J., Pheasant, M., & Mattick, J. S. (2007). The relationship between non-protein-coding DNA and eukaryotic complexity. BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology, 29, 288.Google Scholar
  30. Mehler, M. F., & Mattick, J. S. (2007). Noncoding RNAs and RNA editing in brain development, functional diversification, and neurological disease. Physiological Reviews, 87, 799.Google Scholar
  31. Collins, M. L., et al. (1997). A branched DNA signal amplification assay for quantification of nucleic acid targets below 100 molecules/ml. Nucleic Acids Research, 25, 2979.Google Scholar
  32. Jia, H., et al. (2010). Genome-wide computational identification and manual annotation of human long noncoding RNA genes. Rna, 16, 1478.Google Scholar
  33. Guttman, M., et al. (2009). Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature, 458, 223.Google Scholar
  34. Khalil, A. M., et al. (2009). Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proceedings of the National Academy of Sciences of the United States of America, 106, 11667.Google Scholar
  35. Loewer, S., et al. (2010). Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells. Nature Genetics, 42, 1113.Google Scholar
  36. Harrow, J., et al. (2012). GENCODE: the reference human genome annotation for The ENCODE Project. Genome Research, 22, 1760.Google Scholar
  37. Rinn, J. L., & Chang, H. Y. (2012). Genome regulation by long noncoding RNAs. Annual Review of Biochemistry, 81, 145.PubMedCrossRefGoogle Scholar
  38. Bertone, P., Gerstein, M., & Snyder, M. (2005). Applications of DNA tiling arrays to experimental genome annotation and regulatory pathway discovery. Chromosome Research : An International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology, 13, 259.CrossRefGoogle Scholar
  39. Kapranov, P., et al. (2002) Large-scale transcriptional activity in chromosomes 21 and 22. Science, 296, 916.Google Scholar
  40. Rinn, J. L., et al. (2003), The transcriptional activity of human Chromosome 22. Genes & Development, 17, 529.Google Scholar
  41. Kretz, M., et al. (2012). Suppression of progenitor differentiation requires the long noncoding RNA ANCR. Genes & Development, 26, 338.Google Scholar
  42. Lander E.S., et al. (2001). Initial sequencing and analysis of the human genome. Nature, 409, 860.
  43. Lee, C., & Kikyo, N. (2012). Strategies to identify long noncoding RNAs involved in gene regulation. Cell & Bioscience, 2, 37.CrossRefGoogle Scholar
  44. Trapnell, C., Pachter, L., & Salzberg, S. L. (2009). TopHat: discovering splice junctions with RNA-Seq. Bioinformatics, 25, 1105.Google Scholar
  45. Pauli, A., et al. (2012). Systematic identification of long noncoding RNAs expressed during zebrafish embryogenesis. Genome Research, 22, 577.Google Scholar
  46. Young, R. S., et al. (2012). Identification and properties of 1,119 candidate lincRNA loci in the Drosophila melanogaster genome. Genome Biology and Evolution, 4, 427.PubMedCrossRefGoogle Scholar
  47. de Araujo, M. E., & Huber, L. A. (2007). Subcellular fractionation. Methods in Molecular Biology, 357, 73.PubMedGoogle Scholar
  48. Bhatt, D. M., et al. (2012). Transcript dynamics of proinflammatory genes revealed by sequence analysis of subcellular RNA fractions. Cell, 150, 279.Google Scholar
  49. Tilgner, H., et al. (2012). Deep sequencing of subcellular RNA fractions shows splicing to be predominantly co-transcriptional in the human genome but inefficient for lncRNAs. Genome Research, 22, 1616.Google Scholar
  50. Sleutels, F., Zwart, R., & Barlow, D. P. (2002). The non-coding Air RNA is required for silencing autosomal imprinted genes. Nature, 415, 810.Google Scholar
  51. Mancini-Dinardo, D., Steele, S. J., Levorse, J. M., Ingram, R. S., & Tilghman, S. M. (2006). Elongation of the Kcnq1ot1 transcript is required for genomic imprinting of neighboring genes. Genes & Development, 20, 1268.Google Scholar
  52. Kapranov, P., et al. (2005). Examples of the complex architecture of the human transcriptome revealed by RACE and high-density tiling arrays. Genome Research, 15, 987.Google Scholar
  53. Broadbent, K. M., et al. (2011). A global transcriptional analysis of Plasmodium falciparum malaria reveals a novel family of telomere-associated lncRNAs. Genome Biology, 12, R56.PubMedCrossRefGoogle Scholar
  54. Scotto-Lavino, E., Du, G., & Frohman, M. A. (2006). Amplification of 5’ end cDNA with ‘new RACE’. Nature Protocols, 1, 3056.PubMedCrossRefGoogle Scholar
  55. Shiraki, T., et al. (2003). Cap analysis gene expression for high-throughput analysis of transcriptional starting point and identification of promoter usage. Proceedings of the National Academy of Sciences of the United States of America, 100, 15776.Google Scholar
  56. Valen, E., et al. (2009). Genome-wide detection and analysis of hippocampus core promoters using DeepCAGE. Genome Research, 19, 255.Google Scholar
  57. Djebali, S., et al. (2012). Landscape of transcription in human cells. Nature, 489, 101.Google Scholar
  58. German, M. A., Luo, S., Schroth, G., Meyers, B. C., & Green, P. J. (2009). Construction of Parallel Analysis of RNA Ends (PARE) libraries for the study of cleaved miRNA targets and the RNA degradome. Nature Protocols, 4, 356.PubMedCrossRefGoogle Scholar
  59. Knapp, G. (1989). Enzymatic approaches to probing of RNA secondary and tertiary structure. Methods in Enzymology, 180, 192.PubMedCrossRefGoogle Scholar
  60. Low, J. T., & Weeks, K. M. (2010). SHAPE-directed RNA secondary structure prediction. Methods, 52, 150.Google Scholar
  61. Machado-Lima, A., del Portillo, H. A., & Durham, A. M. (2008). Computational methods in noncoding RNA research. Journal of Mathematical Biology, 56, 15.Google Scholar
  62. Underwood, J. G., et al. (2010). FragSeq: transcriptome-wide RNA structure probing using high-throughput sequencing. Nature Methods, 7, 995.Google Scholar
  63. Reuter, J., & Mathews, D. (2010). RNAstructure: software for RNA secondary structure prediction and analysis. BMC Bioinformatics, 11, 129.PubMedCrossRefGoogle Scholar
  64. Crawford, G. E., et al. (2006). Genome-wide mapping of DNase hypersensitive sites using massively parallel signature sequencing (MPSS). Genome Research, 16, 123.Google Scholar
  65. Reich, D. E., Gabriel, S. B., & Altshuler, D. (2003). Quality and completeness of SNP databases. Nature genetics, 33, 457.Google Scholar
  66. Pasmant, E., et al. (2007). Characterization of a germ-line deletion, including the entire INK4/ARF locus, in a melanoma-neural system tumor family: identification of ANRIL, an antisense noncoding RNA whose expression coclusters with ARF. Cancer Research, 67, 3963.Google Scholar
  67. Barnes, C., et al. (2008). A robust statistical method for case-control association testing with copy number variation. Nature Genetics, 40, 1245.Google Scholar
  68. Sebat, J., et al. (2007). Strong association of de novo copy number mutations with autism. Science, 316, 445.Google Scholar
  69. Mefford, H. C., et al. (2010). Genome-wide copy number variation in epilepsy: novel susceptibility loci in idiopathic generalized and focal epilepsies. PLoS Genetics, 6, e1000962.Google Scholar
  70. Swaminathan, S., et al. (2012). Analysis of copy number variation in Alzheimer’s disease in a cohort of clinically characterized and neuropathologically verified individuals. PLoS ONE, 7, e50640.PubMedCrossRefGoogle Scholar
  71. Hirsch, F. R., et al. (2003). Epidermal growth factor receptor in non-small-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 21, 3798.Google Scholar
  72. Duan, J., Zhang, J. G., Deng, H. W., & Wang, Y. P. (2013). Comparative studies of copy number variation detection methods for next-generation sequencing technologies. PLoS ONE, 8, e59128.PubMedCrossRefGoogle Scholar
  73. Yoon, S., Xuan, Z., Makarov, V., Ye, K., & Sebat, J. (2009). Sensitive and accurate detection of copy number variants using read depth of coverage. Genome Research, 19, 1586.Google Scholar
  74. Moran, V. A., Perera, R. J., & Khalil, A. M. (2012). Emerging functional and mechanistic paradigms of mammalian long non-coding RNAs. Nucleic Acids Research, 40, 6391.Google Scholar
  75. Huarte, M., et al. (2010). A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell, 142, 409.Google Scholar
  76. Kino, T., Hurt, D. E., Ichijo, T., Nader, N., & Chrousos, G. P. (2010). Noncoding RNA gas5 is a growth arrest- and starvation-associated repressor of the glucocorticoid receptor. Science Signaling, 3, ra8.Google Scholar
  77. Niranjanakumari, S., Lasda, E., Brazas, R., & Garcia-Blanco, M. A. (2002). Reversible cross-linking combined with immunoprecipitation to study RNA-protein interactions in vivo. Methods, 26, 182.Google Scholar
  78. Brooks, S. A., & Rigby, W. F. (2000). Characterization of the mRNA ligands bound by the RNA binding protein hnRNP A2 utilizing a novel in vivo technique. Nucleic Acids Research, 28, E49.Google Scholar
  79. Mili, S., & Steitz, J. A. (2004). Evidence for reassociation of RNA-binding proteins after cell lysis: implications for the interpretation of immunoprecipitation analyses. Rna, 10, 1692.Google Scholar
  80. Collins, K. (2008). Physiological assembly and activity of human telomerase complexes. Mechanisms of Ageing and Development, 129, 91.Google Scholar
  81. Heyne, S., Costa, F., Rose, D., & Backofen, R. (2012). GraphClust: alignment-free structural clustering of local RNA secondary structures. Bioinformatics, 28, i224.Google Scholar
  82. Selth, L. A., Gilbert, C., & Svejstrup, J. Q. (2009). RNA immunoprecipitation to determine RNA-protein associations in vivo. Cold Spring Harbor protocols, 2009, pdb prot5234.Google Scholar
  83. Licatalosi, D. D., et al. (2008). HITS-CLIP yields genome-wide insights into brain alternative RNA processing. Nature, 456, 464.Google Scholar
  84. Ule, J., Jensen, K., Mele, A., & Darnell, R. B. (2005). CLIP: a method for identifying protein-RNA interaction sites in living cells. Methods, 37, 376.Google Scholar
  85. Guil, S., et al. (2012). Intronic RNAs mediate EZH2 regulation of epigenetic targets. Nature Structural & Molecular Biology, 19, 664.Google Scholar
  86. Sparmann, A., & van Lohuizen, M. (2006). Polycomb silencers control cell fate, development and cancer. Nature Reviews. Cancer, 6, 846.Google Scholar
  87. Chase, A., & Cross, N. C. (2011). Aberrations of EZH2 in cancer. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 17, 2613.Google Scholar
  88. Bu, D., et al. (2012). NONCODE v3.0: integrative annotation of long noncoding RNAs. Nucleic Acids Research, 40, D210.Google Scholar
  89. Konig, J., Zarnack, K., Luscombe, N. M., & Ule, J. (2011). Protein-RNA interactions: new genomic technologies and perspectives. Nature Reviews. Genetics, 13, 77.Google Scholar
  90. Hafner, M., et al. (2010). Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP. Cell, 141, 129.Google Scholar
  91. Konig, J., et al. (2010). iCLIP reveals the function of hnRNP particles in splicing at individual nucleotide resolution. Nature Structural & Molecular Biology, 17, 909.Google Scholar
  92. Yap, K. L., et al. (2010). Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. Molecular Cell, 38, 662.Google Scholar
  93. Bertani, S., Sauer, S., Bolotin, E., & Sauer, F. (2011). The noncoding RNA Mistral activates Hoxa6 and Hoxa7 expression and stem cell differentiation by recruiting MLL1 to chromatin. Molecular Cell, 43, 1040.Google Scholar
  94. Chu, C., Qu, K., Zhong, F. L., Artandi, S. E., & Chang, H. Y. (2011). Genomic maps of long noncoding RNA occupancy reveal principles of RNA-chromatin interactions. Molecular Cell, 44, 667.Google Scholar
  95. Guttman, M., & Rinn, J. L. (2012). Modular regulatory principles of large non-coding RNAs. Nature, 482, 339.Google Scholar
  96. Lucchesi, J. C., Kelly, W. G., & Panning, B. (2005). Chromatin remodeling in dosage compensation. Annual Review of Genetics, 39, 615.PubMedCrossRefGoogle Scholar
  97. Alekseyenko, A. A., et al. (2008) A sequence motif within chromatin entry sites directs MSL establishment on the Drosophila X chromosome. Cell, 134, 599.Google Scholar
  98. Chu, C., Quinn, J., & Chang, H. Y. (2012). Chromatin isolation by RNA purification (ChIRP). Journal of Visualized Experiments: JoVE.Google Scholar
  99. Guttman, M., et al. lincRNAs act in the circuitry controlling pluripotency and differentiation. Nature, 477, 295.Google Scholar
  100. McCarthy, N. (2012). Epigenetics. Going places with BANCR. Nature Reviews. Cancer, 12, 451.Google Scholar
  101. Chakraborty, D., et al. (2012). Combined RNAi and localization for functionally dissecting long noncoding RNAs. Nature Methods, 9, 360.Google Scholar
  102. Guttman, M., et al. (2010). Ab initio reconstruction of cell type-specific transcriptomes in mouse reveals the conserved multi-exonic structure of lincRNAs. Nature Biotechnology, 28, 503.Google Scholar
  103. Liao, Q., et al. (2011). ncFANs: a web server for functional annotation of long non-coding RNAs. Nucleic Acids Research, 39, W118.Google Scholar
  104. Grossman, S. R., et al. (2013). Identifying recent adaptations in large-scale genomic data. Cell, 152, 703.Google Scholar
  105. Siepel, A., et al. (2005). Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Research, 15, 1034.Google Scholar
  106. Benelli, M., et al. (2012). Discovering chimeric transcripts in paired-end RNA-seq data by using EricScript. Bioinformatics, 28, 3232.Google Scholar
  107. Risueno, A., Fontanillo, C., Dinger, M. E., & De Las Rivas, J. (2010). GATExplorer: genomic and transcriptomic explorer; mapping expression probes to gene loci, transcripts, exons and ncRNAs. BMC Bioinformatics, 11, 221.PubMedCrossRefGoogle Scholar
  108. Bao, M., Cervantes Cervantes, M., Zhong, L., & Wang, J. T. (2012). Searching for non-coding RNAs in genomic sequences using ncRNAscout. Genomics, Proteomics & Bioinformatics, 10, 114.Google Scholar
  109. Salari, R., et al. (2009). smyRNA: a novel Ab initio ncRNA gene finder. PLoS ONE, 4, e5433.PubMedCrossRefGoogle Scholar
  110. Wang, L., et al. (2013). CPAT: Coding-Potential Assessment Tool using an alignment-free logistic regression model. Nucleic Acids Research, 41, e74.Google Scholar
  111. Lin, M. F., Jungreis, I., & Kellis, M. (2011). PhyloCSF: a comparative genomics method to distinguish protein coding and non-coding regions. Bioinformatics, 27, i275.Google Scholar
  112. Tabei, Y., Kiryu, H., Kin, T., & Asai, K. (2008). A fast structural multiple alignment method for long RNA sequences. BMC Bioinformatics, 9, 33.PubMedCrossRefGoogle Scholar
  113. McCallum, K. J., & Wang, J. P. (2013). Quantifying copy number variations using a hidden Markov model with inhomogeneous emission distributions. Biostatistics, 14, 600.Google Scholar
  114. Fiegler, H., et al. (2006). Accurate and reliable high-throughput detection of copy number variation in the human genome. Genome Research, 16, 1566.Google Scholar
  115. Glessner, J. T., Li, J., & Hakonarson, H. (2013). ParseCNV integrative copy number variation association software with quality tracking. Nucleic Acids Research, 41, e64.Google Scholar
  116. Szymanski, M., Erdmann, V. A., & Barciszewski, J. (2003). Noncoding regulatory RNAs database. Nucleic Acids Research, 31, 429.Google Scholar
  117. Da Sacco, L., Baldassarre, A., & Masotti, A. (2012). Bioinformatics Tools and Novel Challenges in Long Non-Coding RNAs (lncRNAs) Functional Analysis. International Journal of Molecular Sciences, 13, 97.PubMedCrossRefGoogle Scholar
  118. Paschoal, A. R., et al. (2012). Non-coding transcription characterization and annotation: A guide and web resource for non-coding RNA databases. RNA Biology, 9, 274.Google Scholar
  119. Amaral, P. P., Clark, M. B., Gascoigne, D. K., Dinger, M. E., & Mattick, J. S. (2011). lncRNAdb: a reference database for long noncoding RNAs. Nucleic Acids Research 39, D146.Google Scholar
  120. Mituyama, T., et al. (2009). The Functional RNA Database 3.0: databases to support mining and annotation of functional RNAs. Nucleic Acids Research, 37, D89.Google Scholar
  121. Bu, D., et al. (2011). NONCODE v3.0: integrative annotation of long noncoding RNAs. Nucleic Acids Research, 39, d146–d151.Google Scholar
  122. Burge, S. W., et al. (2012). Rfam 11.0: 10 years of RNA families. Nucleic Acids Research, 41, D226.Google Scholar
  123. Dinger, M. E., et al. (2009). NRED: a database of long noncoding RNA expression. Nucleic Acids Research, 37, D122.Google Scholar
  124. Wu, T., et al. (2006). NPInter: the noncoding RNAs and protein related biomacromolecules interaction database. Nucleic Acids Research, 34, D150.Google Scholar
  125. Yang, J.-H., Li, J.-H., Jiang, S., Zhou, H., & Qu, L.-H. (2012). ChIPBase: a database for decoding the transcriptional regulation of long non-coding RNA and microRNA genes from ChIP-Seq data. Nucleic Acids Research, 41, D177.Google Scholar
  126. Yamasaki, C., et al. (2009). H-InvDB in 2009: extended database and data mining resources for human genes and transcripts. Nucleic Acids Research, 38, D626.Google Scholar
  127. Szymański, M., Erdmann, V. A., & Barciszewski, J. (2003). Noncoding regulatory RNAs database. Nucleic Acids Research, 31, 429.Google Scholar
  128. Niazi, F., & Valadkhan, S. (2012). Computational analysis of functional long noncoding RNAs reveals lack of peptide-coding capacity and parallels with 3’ UTRs. Rna, 18, 825.Google Scholar
  129. Volders, P.-J., et al. LNCipedia: a database for annotated human lncRNA transcript sequences and structures. Nucleic Acids Research, 41, D246.Google Scholar
  130. Chen, G., et al. (2013). LncRNADisease: a database for long-non-coding RNA-associated diseases. Nucleic Acids Research, 41, D983.Google Scholar
  131. Paraskevopoulou, M. D., et al. (2013). DIANA-LncBase: experimentally verified and computationally predicted microRNA targets on long non-coding RNAs. Nucleic Acids Research, 41, D239.Google Scholar
  132. Belinky, F., et al. (2013). Non-redundant compendium of human ncRNA genes in GeneCards. Bioinformatics, 29, 255.Google Scholar
  133. Jin, J., Liu, J., Wang, H., Wong, L., & Chua, N.-H. (2013). PLncDB: plant long non-coding RNA database. Bioinformatics, 29, 1068.Google Scholar
  134. Sun, K., et al. (2013). iSeeRNA: identification of long intergenic non-coding RNA transcripts from transcriptome sequencing data. BMC Genomics, 14, 1.Google Scholar
  135. Gellert, P., Ponomareva, Y., Braun, T., & Uchida, S. (2013). Noncoder: a web interface for exon array-based detection of long non-coding RNAs. Nucleic Acids Research, 41, e20.Google Scholar
  136. Chen, C.-J., et al. (2012). ncPRO-seq: a tool for annotation and profiling of ncRNAs in sRNA-seq data. Bioinformatics, 28, 3147.Google Scholar
  137. Chang, T.-H., et al. (2013). An enhanced computational platform for investigating the roles of regulatory RNA and for identifying functional RNA motifs. BMC Bioinformatics, 14, 1.Google Scholar
  138. Wright, M. W., & Bruford, E. A. (2011). Naming ‘junk’: human non-protein coding RNA (ncRNA) gene nomenclature. Human Genomics, 5, 90.Google Scholar
  139. Sun, L., et al. (2012). Prediction of novel long non-coding RNAs based on RNA-Seq data of mouse Klf1 knockout study. BMC Bioinformatics, 13, 331.PubMedCrossRefGoogle Scholar
  140. Jeggari, A., Marks, D. S., & Larsson, E. (2012). miRcode: a map of putative microRNA target sites in the long non-coding transcriptome. Bioinformatics, 28, 2062–2063. Google Scholar
  141. Beck, A. H., et al. (2010). 3′-end sequencing for expression quantification (3SEQ) from archival tumor samples. PLoS ONE, 5, e8768.PubMedCrossRefGoogle Scholar
  142. Brunner, A. L., et al. (2012). Transcriptional profiling of long non-coding RNAs and novel transcribed regions across a diverse panel of archived human cancers. Genome Biology, 13, R75.Google Scholar
  143. Kertesz, M., et al. (2010). Genome-wide measurement of RNA secondary structure in yeast. Nature, 467, 103.Google Scholar
  144. Spitale, R. C., et al. (2010). RNA SHAPE analysis in living cells. Nature Chemical Biology, 9, 18.Google Scholar
  145. Wang, Y., Zheng, D., Tan, Q., Wang, M. X., & Gu, L. Q. (2011). Nanopore-based detection of circulating microRNAs in lung cancer patients. Nature Nanotechnology, 6, 668.Google Scholar
  146. Wanunu, M., et al. Rapid electronic detection of probe-specific microRNAs using thin nanopore sensors. Nature Nanotechnology, 5, 807.Google Scholar
  147. Dong, H., et al. (2012). Highly sensitive multiple microRNA detection based on fluorescence quenching of graphene oxide and isothermal strand-displacement polymerase reaction. Analytical Chemistry, 84, 4587.Google Scholar
  148. Neely, L. A., et al. (2006). A single-molecule method for the quantitation of microRNA gene expression. Nature Methods, 3, 41.Google Scholar
  149. Cissell, K. A., Rahimi, Y., Shrestha, S., Hunt, E. A., & Deo, S. K. (2008). Bioluminescence-based detection of microRNA, miR21 in breast cancer cells. Analytical Chemistry, 80, 2319.Google Scholar
  150. Zhang, G. J., Chua, J. H., Chee, R. E., Agarwal, A., & Wong, S. M. (2009). Label-free direct detection of MiRNAs with silicon nanowire biosensors. Biosensors & Bioelectronics, 24, 2504.Google Scholar
  151. Sioss, J. A., et al. (2012). Nanoresonator chip-based RNA sensor strategy for detection of circulating tumor cells: response using PCA3 as a prostate cancer marker. Nanomedicine : Nanotechnology, Biology, and Medicine, 8, 1017.Google Scholar
  152. Driskell, J. D., Primera-Pedrozo, O. M., Dluhy, R. A., Zhao, Y., & Tripp, R. A. (2009). Quantitative surface-enhanced Raman spectroscopy based analysis of microRNA mixtures. Applied Spectroscopy, 63, 1107.Google Scholar
  153. Fang, S., Lee, H. J., Wark, A. W., & Corn, R. M. (2006). Attomole microarray detection of microRNAs by nanoparticle-amplified SPR imaging measurements of surface polyadenylation reactions. Journal of the American Chemical Society, 128, 14044.Google Scholar
  154. Nasheri, N., et al. (2011). An enzyme-linked assay for the rapid quantification of microRNAs based on the viral suppressor of RNA silencing protein p19. Analytical Biochemistry, 412, 165.Google Scholar
  155. Sipova, H., et al. (2010). Surface plasmon resonance biosensor for rapid label-free detection of microribonucleic acid at subfemtomole level. Analytical Chemistry, 82, 10110.Google Scholar
  156. Wark, A. W., Lee, H. J., & Corn, R. M. (2008). Multiplexed detection methods for profiling microRNA expression in biological samples. Angewandte Chemie, 47, 644.PubMedCrossRefGoogle Scholar
  157. Gao, Z., & Yu, Y. H. (2007). Direct labeling microRNA with an electrocatalytic moiety and its application in ultrasensitive microRNA assays. Biosensors & Bioelectronics, 22, 933.Google Scholar
  158. Gao, Z., & Yang, Z. (2006). Detection of MicroRNAs Using Electrocatalytic Nanoparticle Tags. Analytical Chemistry, 78, 1470.Google Scholar
  159. Peng, Y., & Gao, Z. (2011). Amplified detection of microRNA based on ruthenium oxide nanoparticle-initiated deposition of an insulating film. Analytical Chemistry, 83, 820.Google Scholar
  160. Cissell, K. A., & Deo, S. K. (2009). Trends in microRNA detection. Analytical and Bioanalytical Chemistry, 394, 1109.Google Scholar
  161. Alhasan, A. H., et al. (2012). Scanometric microRNA array profiling of prostate cancer markers using spherical nucleic acid-gold nanoparticle conjugates. Analytical Chemistry, 84, 4153.Google Scholar
  162. Chan, H. M., Chan, L. S., Wong, R. N., & Li, H. W. (2010). Direct quantification of single-molecules of microRNA by total internal reflection fluorescence microscopy. Analytical Chemistry 82, 6911.Google Scholar
  163. Meldrum, D. (2000a). Automation for genomics, part one: preparation for sequencing. Genome Research 10, 1081.Google Scholar
  164. Meldrum, D. (2000b). Automation for genomics, part two: sequencers, microarrays, and future trends. Genome Research, 10, 1288.Google Scholar
  165. Ramskold, D., et al. (2012). Full-length mRNA-Seq from single-cell levels of RNA and individual circulating tumor cells. Nature Biotechnology, 30, 777.Google Scholar
  166. Mustafi, D., et al. (2013). Evolutionarily conserved long intergenic noncoding RNAs in the eye. Human Molecular Genetics, 22, 2992.Google Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Fereshteh Jahaniani
    • 1
  • Varsha Rao
    • 1
  • Stephanie Nevins
    • 1
  • Damek Spacek
    • 1
  • Neal Bharadwaj
    • 1
  • Jason Reuter
    • 1
  • Michael Snyder
    • 1
  1. 1.Department of GeneticsStanford UniversityStanfordUSA

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